Angiotensin II type 2 receptor deficiency exacerbates heart failure and reduces survival after acute myocardial infarction in mice

Background-Angiotensin II plays a prominent role in the progression of heart failure after acute myocardial infarction (AMI). Although both angiotensin type 1 (AT(1)) and type 2 (AT(2)) receptors are known to be present in the heart, comparatively little is known about the latter. We therefore examined the role played by AT(2) receptors in post-AMI heart failure. Methods and Results-In wild-type mice subjected to AMI by coronary artery ligation, AT(2) receptor immunoreactivity is upregulated in the infarct and border areas. Among AT2 receptor-null (-/-) mice, the 7-day survival rate after AMI was significantly lower than among wild-type mice (43% versus 67%; P<0.05). All sham-operated animals of both genotypes survived through the study. Ventricular mRNA levels for brain natriuretic peptide were elevated in both genotypes 24 hours after coronary occlusion, with levels in AT(2)(-/-) significantly higher than in wild-type mice, as were their lung weights, and histological examination revealed marked pulmonary congestion in the AT(2)(-/-) mice. Cardiac function was significantly decreased in AT(2)(-/-) mice 2 days after AMI. Conclusions-AT(2) receptor deficiency exacerbates short-term death rates and heart failure after experimental AMI in mice. The AT(2) receptor may thus exert a protective effect on the heart after AMI.